Effects of repeated phencyclidine treatment on serotonin transporter in rat brain.

Repeated treatment with phencyclidine (PCP) over 14 days at 7.5 mg/kg per day significantly reduced the frequency of backpedalling, a serotonergic stereotyped behavior, indicating tolerance. This repeated treatment also decreased the equilibrium dissociation constant (Kd) of [3H]paroxetine binding to serotonin transporters in whole brain excluding the cerebellum, without changing the maximum number of binding sites (Bmax). A single PCP treatment did not alter binding parameters. The results suggest that repeated PCP treatment induces tolerance in serotonergic stereotyped behavior and increases the affinity of serotonin transporters, possibly as a compensatory response to chronic inhibition of serotonin uptake.

Study at a glance

Abstract

Phencyclidine (PCP) is known to be an inhibitor of serotonin (5-HT) uptake and to increase serotonergic activity. The development of tolerance to serotonergic stereotyped behaviors induced by repeated PCP treatment and changes of 5-HT transporters were examined. Backpedalling was significantly reduced in frequency following 14 days PCP treatment (7.5 mg/kg per day). Furthermore, repeated PCP treatment decreased the equilibrium dissociation constant (Kd) of [3H]paroxetine binding to 5-HT transporters in whole brain excluding the cerebellum without any change of maximum number of binding sites (Bmax). Single treatment with PCP failed to change binding parameters. These results indicate that repeated PCP treatment causes tolerance in serotonergic stereotyped behavior and increases affinity of 5-HT transporters for [3H]paroxetine binding. The increased affinity of 5-HT transporters could represent compensatory responses to chronic inhibition of 5-HT uptake by PCP.